BACKGROUND: IL-13Ra2 is overexpressed by gliomas but not by normal tissue. However, the molecular basis for IL-13Ra2 overexpression in gliomas is unknown. METHODS: In the present study we have investigated the regulatory mechanisms that are responsible for the expression of IL-13Ra2 with mutation analysis, quantitative RT-PCR, Flow cytometry analysis, transcription factor binding assay and Elisa. RESULTS: Our results reveal a complex mechanism for regulating IL-13Ra2 expression that involves at least 2 promoters and 4 transcripts of human IL-13Ra2. Transcription factors NFAT and AP1 are necessary and essential for the expression of this GBM related transcript, and are responsible for the high level of expression of IL-13Ra2 in GBM. Most interestingly, we found that expression of this transcript results in the production of a secreted form of IL-13Ra2 and thus may have the potential to be used as a diagnostic biomarker for GBM patients and other cancer patients that express the soluble form of this receptor. CONCLUSION: This study is the first to characterize the role of NFAT and AP1 in the regulation of IL-13Ra2 expression, and provides insight into understanding the high levels of IL-13Ra2 expressed by GBM cells.
BACKGROUND:IL-13Ra2 is overexpressed by gliomas but not by normal tissue. However, the molecular basis for IL-13Ra2 overexpression in gliomas is unknown. METHODS: In the present study we have investigated the regulatory mechanisms that are responsible for the expression of IL-13Ra2 with mutation analysis, quantitative RT-PCR, Flow cytometry analysis, transcription factor binding assay and Elisa. RESULTS: Our results reveal a complex mechanism for regulating IL-13Ra2 expression that involves at least 2 promoters and 4 transcripts of humanIL-13Ra2. Transcription factors NFAT and AP1 are necessary and essential for the expression of this GBM related transcript, and are responsible for the high level of expression of IL-13Ra2 in GBM. Most interestingly, we found that expression of this transcript results in the production of a secreted form of IL-13Ra2 and thus may have the potential to be used as a diagnostic biomarker for GBM patients and other cancerpatients that express the soluble form of this receptor. CONCLUSION: This study is the first to characterize the role of NFAT and AP1 in the regulation of IL-13Ra2 expression, and provides insight into understanding the high levels of IL-13Ra2 expressed by GBM cells.
Authors: Nai-Ming Chen; Garima Singh; Alexander Koenig; Geou-Yarh Liou; Peter Storz; Jin-San Zhang; Lisanne Regul; Sankari Nagarajan; Benjamin Kühnemuth; Steven A Johnsen; Matthias Hebrok; Jens Siveke; Daniel D Billadeau; Volker Ellenrieder; Elisabeth Hessmann Journal: Gastroenterology Date: 2015-01-23 Impact factor: 22.682
Authors: Hang Chang; Gerald V Fontenay; Ju Han; Ge Cong; Frederick L Baehner; Joe W Gray; Paul T Spellman; Bahram Parvin Journal: BMC Bioinformatics Date: 2011-12-20 Impact factor: 3.169